Summary ? Core B (Preclinical Therapeutics) The Preclinical Therapeutics Core will leverage the expertise and infrastructure of the Center for Molecular Therapeutics at the Massachusetts General Hospital and of the Center for Co-Clinical Trials at the MD Anderson Cancer Center. High throughput drug screening of established and project derived cells representing the array of PDAC subtypes will be performed. A curated collection of clinically relevant compounds as well as novel compounds specifically relevant to the projects will be used in 2D and 3D cell viability assays using defined metabolic conditions. Signaling pathway and immune-modulator measurements will also be performed to inform mechanism of action and evaluate the impact of treatments on the interaction between PDAC cells and the immune system. Data that emerge from in vitro screens will be prioritized for in vivo efficacy studies at the Center for Co-Clinical Trials. Here, a dedicated pharmacology staff will evaluate single agents or drug combinations in the most relevant pre-clinical PDAC models, including human PDx and autochthonous GEM models. Through comprehensive pharmacologic analyses, the Core B aims to evaluate novel therapeutic approaches and define biomarkers that may predict responsiveness in clinical trials.